Hypertension Guidelines: Same Data, Different Conclusions
Hypertension Guidelines: Same Data, Different Conclusions
Henry R. Black, MD: Hi. I'm Dr. Henry Black. I'm an adjunct professor of medicine at the Langone NYU School of Medicine and a former president of the American Society of Hypertension. I'm here today with 2 of my colleagues. Michael, would you introduce yourself?
Michael A. Weber, MD: Yes. I'm Michael Weber. I'm a professor of medicine at State University of New York Downstate College of Medicine and the editor of the Journal of Clinical Hypertension.
Dr. Black: Ray?
Raymond R. Townsend, MD: I'm a professor of medicine at the University of Pennsylvania. I carry a card that says I'm a nephrologist but I mostly do hypertension care. I was lately part of the appointed JNC 8 panel and also served on the US advisory board for the Medtronic SYMPLICITY-HTN 3 hypertension trial, and I'm current vice president of the American Society of Hypertension (ASH).
Dr. Black: One of the things I want to talk about today is guidelines. Both of you have authored and been part of guideline committees. I was part of the so-called JNC 6 and JNC 7 but not a part of JNC 8. So, Michael, could you review what your guideline said and where it came from?
Dr. Weber: Yes. I was involved as the coordinator of a large group of expert authors of the ASH and the International Society of Hypertension (ISH) guidelines. They were written primarily to provide what you might call a curriculum on how to manage hypertension in the community. That said, they were very much based on the available evidence, so they do constitute guidelines. But we wrote them in such a way as to be easily usable by people working on the frontlines of medicine.
Dr. Black: Ray, what about JNC 8, which, by the way, I'm not sure should be called JNC 8. The Joint National Committees were appointed by the National High Blood Pressure Education Program, and that was disbanded several years ago. So how come you can still call yourself JNC 8?
Dr. Townsend: Well, if I understand the phenomenon correctly, Henry, the National Heart, Lung, and Blood Institute (NHLBI) actually convened this panel. My understanding is that they convened several of the previous Joint National Committee panels as well.
Dr. Black: All of them, in fact.
Dr. Townsend: Exactly. So we really saluted the NHLBI in 2008 when the 18 or so of us were first put in a room in Bethesda and were charged with writing the next hypertension guideline in the United States -- and to do it in a somewhat different manner such that it would be entirely, to the best it can be, evidence-based as opposed to being consensus-based. At least that was the charge that we were given in September 2008 when we first met.
Dr. Black: I'd like to talk about that a little bit. You had 11 recommendations, I believe, in what was published. Six of them -- more than half -- ended up as expert opinion anyway. How come that happened? Why were so few recommendations based on trial evidence?
Dr. Townsend: We began the process in the JNC 8 by developing what were called the critical questions. We came up with 23 critical questions from our parlay with the various primary care doctors in our various institutions across the country. We felt that these were pretty important questions in the current management and evaluation of blood pressure. We couldn't do 23 questions so we decided on 5, and of those 5, the 3 most critical ones are the core of what became the US guidelines in 2014 by the panel appointed to the Joint National Committee. The issues that we faced with respect to making the recommendations began first with the summation of the evidence. So each of the questions that we developed for JNC 8 had to have a certain process laid out by which a query was made through all of the different databases. It wasn't just a PubMed search; this was fully vetted, and all the background information is available. You will see that we searched a wide range of sources.
Once the question was written and we had the data back, we had to manually go through the thousands of hits that we got through the process and grade them based upon preset criteria for what is an acceptable-, good-, fair-, or poor-quality randomized clinical trial. We consciously made the choice from the get-go that we would only accept clinical trial evidence for the report itself. We looked at meta-analyses. We looked at other things. But for distilling it down to what became the evidence base, we only used randomized clinical trials. That's been a difference, for example, between our approach and the European approach.
Dr. Black: How about yours, Michael? How different was what you did in your report, which I won't call a guideline?
Dr. Weber: Well, it was intended to be more than just a report, but that said, it's strange that we were influenced predominantly by the same trials that the JNC 8 panelists were influenced by. In other words, we looked at SHEP. We looked at Syst-Eur. We looked at HYVET. We looked at all of the studies that we're all very familiar with and decided how to be influenced. We were more liberal, though. We were not as rigid (or as meticulous, depending on which word you want to use), as the JNC 8 group. We were willing to be influenced by what we thought was credible and useful information. Ray, in the end, wasn't your dilemma that you wanted it to be evidence-based rather than consensus-based? But when the evidence wasn't as complete as it should have been to answer these questions, you didn't have a consensus and you didn't quite have the evidence you wanted. You must have been aware that it was a difficult assignment. The further you went into it, you must have become aware that it was getting harder and harder to do what you had set out to do.
Dr. Townsend: Of course. The other charge we had, besides writing a guideline based on evidence, was to identify gaps in the knowledge base. We felt that that was one of the contributions that we should make as a group after sifting through what amounted to mountains of information, much of which was chaff and not wheat. The number of really useful trials that are rigorous enough to come to a conclusion that helped us define what is and what is not elevated blood pressure. When does the risk of treating it exceed the risks of benefit so that we have a cut-off for what is and is not hypertension? What goal should we treat blood pressure to? How should we do that with medication? Those were the 3 critical questions that we came down to, but one of the problems that we faced -- and we all knew this going in -- is that we have fairly good evidence for diastolic blood pressure thresholds and diastolic blood pressure treatment goals. However, there is very little on systolic, aside from the 160 mm Hg and higher that was popularized in the late '80s when SHEP, Syst-Eur, STONE, Syst-China, HYVET, and all of the other trials were either in their pilot phase or actually in their full clinical trial stage. What we lacked was really definitive evidence on the 140-160 mm Hg range for systolic blood pressure, particularly in the population at greatest risk of having that kind of blood pressure: those who are 60 years of age and older.
JNC 8 Guideline
Henry R. Black, MD: Hi. I'm Dr. Henry Black. I'm an adjunct professor of medicine at the Langone NYU School of Medicine and a former president of the American Society of Hypertension. I'm here today with 2 of my colleagues. Michael, would you introduce yourself?
Michael A. Weber, MD: Yes. I'm Michael Weber. I'm a professor of medicine at State University of New York Downstate College of Medicine and the editor of the Journal of Clinical Hypertension.
Dr. Black: Ray?
Raymond R. Townsend, MD: I'm a professor of medicine at the University of Pennsylvania. I carry a card that says I'm a nephrologist but I mostly do hypertension care. I was lately part of the appointed JNC 8 panel and also served on the US advisory board for the Medtronic SYMPLICITY-HTN 3 hypertension trial, and I'm current vice president of the American Society of Hypertension (ASH).
Dr. Black: One of the things I want to talk about today is guidelines. Both of you have authored and been part of guideline committees. I was part of the so-called JNC 6 and JNC 7 but not a part of JNC 8. So, Michael, could you review what your guideline said and where it came from?
Dr. Weber: Yes. I was involved as the coordinator of a large group of expert authors of the ASH and the International Society of Hypertension (ISH) guidelines. They were written primarily to provide what you might call a curriculum on how to manage hypertension in the community. That said, they were very much based on the available evidence, so they do constitute guidelines. But we wrote them in such a way as to be easily usable by people working on the frontlines of medicine.
Dr. Black: Ray, what about JNC 8, which, by the way, I'm not sure should be called JNC 8. The Joint National Committees were appointed by the National High Blood Pressure Education Program, and that was disbanded several years ago. So how come you can still call yourself JNC 8?
Dr. Townsend: Well, if I understand the phenomenon correctly, Henry, the National Heart, Lung, and Blood Institute (NHLBI) actually convened this panel. My understanding is that they convened several of the previous Joint National Committee panels as well.
Dr. Black: All of them, in fact.
Dr. Townsend: Exactly. So we really saluted the NHLBI in 2008 when the 18 or so of us were first put in a room in Bethesda and were charged with writing the next hypertension guideline in the United States -- and to do it in a somewhat different manner such that it would be entirely, to the best it can be, evidence-based as opposed to being consensus-based. At least that was the charge that we were given in September 2008 when we first met.
Dr. Black: I'd like to talk about that a little bit. You had 11 recommendations, I believe, in what was published. Six of them -- more than half -- ended up as expert opinion anyway. How come that happened? Why were so few recommendations based on trial evidence?
Dr. Townsend: We began the process in the JNC 8 by developing what were called the critical questions. We came up with 23 critical questions from our parlay with the various primary care doctors in our various institutions across the country. We felt that these were pretty important questions in the current management and evaluation of blood pressure. We couldn't do 23 questions so we decided on 5, and of those 5, the 3 most critical ones are the core of what became the US guidelines in 2014 by the panel appointed to the Joint National Committee. The issues that we faced with respect to making the recommendations began first with the summation of the evidence. So each of the questions that we developed for JNC 8 had to have a certain process laid out by which a query was made through all of the different databases. It wasn't just a PubMed search; this was fully vetted, and all the background information is available. You will see that we searched a wide range of sources.
Once the question was written and we had the data back, we had to manually go through the thousands of hits that we got through the process and grade them based upon preset criteria for what is an acceptable-, good-, fair-, or poor-quality randomized clinical trial. We consciously made the choice from the get-go that we would only accept clinical trial evidence for the report itself. We looked at meta-analyses. We looked at other things. But for distilling it down to what became the evidence base, we only used randomized clinical trials. That's been a difference, for example, between our approach and the European approach.
ASH/ISH Guidance
Dr. Black: How about yours, Michael? How different was what you did in your report, which I won't call a guideline?
Dr. Weber: Well, it was intended to be more than just a report, but that said, it's strange that we were influenced predominantly by the same trials that the JNC 8 panelists were influenced by. In other words, we looked at SHEP. We looked at Syst-Eur. We looked at HYVET. We looked at all of the studies that we're all very familiar with and decided how to be influenced. We were more liberal, though. We were not as rigid (or as meticulous, depending on which word you want to use), as the JNC 8 group. We were willing to be influenced by what we thought was credible and useful information. Ray, in the end, wasn't your dilemma that you wanted it to be evidence-based rather than consensus-based? But when the evidence wasn't as complete as it should have been to answer these questions, you didn't have a consensus and you didn't quite have the evidence you wanted. You must have been aware that it was a difficult assignment. The further you went into it, you must have become aware that it was getting harder and harder to do what you had set out to do.
Dr. Townsend: Of course. The other charge we had, besides writing a guideline based on evidence, was to identify gaps in the knowledge base. We felt that that was one of the contributions that we should make as a group after sifting through what amounted to mountains of information, much of which was chaff and not wheat. The number of really useful trials that are rigorous enough to come to a conclusion that helped us define what is and what is not elevated blood pressure. When does the risk of treating it exceed the risks of benefit so that we have a cut-off for what is and is not hypertension? What goal should we treat blood pressure to? How should we do that with medication? Those were the 3 critical questions that we came down to, but one of the problems that we faced -- and we all knew this going in -- is that we have fairly good evidence for diastolic blood pressure thresholds and diastolic blood pressure treatment goals. However, there is very little on systolic, aside from the 160 mm Hg and higher that was popularized in the late '80s when SHEP, Syst-Eur, STONE, Syst-China, HYVET, and all of the other trials were either in their pilot phase or actually in their full clinical trial stage. What we lacked was really definitive evidence on the 140-160 mm Hg range for systolic blood pressure, particularly in the population at greatest risk of having that kind of blood pressure: those who are 60 years of age and older.
